Monte Carlo evaluation of radionuclides for early brain metastases targeting

Metastasis of breast cancer to the brain presents a pressing therapeutic challenge. Vascular cell adhesion molecule 1 (VCAM‐1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. We have developed a Monte Carlo model representing brain vasculature to evaluate the efficacy of a variety of potential therapeutic nuclides; alpha‐emitters: 149Tb, 211At, 212Pb, 213Bi and 225Ac; beta and Auger electron‐emitters: 90Y, 161Tb and 177Lu, 67Ga, 89Zr, 111In and 124I for targeted radionuclide therapy (TRT)

Monte Carlo evaluation of radionuclides for early brain metastases targeting

Metastasis of breast cancer to the brain presents a pressing therapeutic challenge. Vascular cell adhesion molecule 1 (VCAM‐1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. We have developed a Monte Carlo model representing brain vasculature to evaluate the efficacy of a variety of potential therapeutic nuclides; alpha‐emitters: 149Tb, 211At, 212Pb, 213Bi and 225Ac; beta and Auger electron‐emitters: 90Y, 161Tb and 177Lu, 67Ga, 89Zr, 111In and 124I for targeted radionuclide therapy (TRT)

Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy in an early brain metastasis model

Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of α-emitting radionuclides, 149Tb, 211At, 212Pb, 213Bi and 225Ac; β-emitting radionuclides, 90Y, 161Tb and 177Lu; and Auger electron (AE)-emitters 67Ga, 89Zr, 111In and 124I, for targeted radionuclide therapy (TRT). METHODS: Histologic sections and two photon microscopy of mouse brain parenchyma were used to inform a cylindrical vessel geometry using the Geant4 general purpose Monte Carlo (MC) toolkit with the Geant4-DNA low energy physics models. Energy deposition was evaluated as a radial function and the resulting phase spaces were superimposed on a DNA model to estimate double-strand break (DSB) yields for representative β- and α-emitters, 177Lu and 212Pb. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions. RESULTS: 177Lu produced 2.69 ± 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 μm. The DSB yield of 212Pb included two local maxima produced by the 6.1 MeV and 8.8 MeV α-emissions from decay products, 212Bi and 212Po, with yields of 7.64 ± 0.12 and 9.15 ± 0.24 per GbpGy, respectively. Given its higher DSB yield 212Pb may be more effective for short range targeting of early micrometastatic lesions than 177Lu. CONCLUSION: MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of α-, β- and AE-emitting radionuclides for TRT. 212Pb, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.</p